Increase In Plasma Free Hemoglobin Research Articles

A Murine Model of Veno-Arterial Extracorporeal Membrane Oxygenation.

The mechanisms driving the pathologic state created by extracorporeal membrane oxygenation (ECMO) remain poorly defined. We developed the first complete blood-primed murine model of veno-arterial ECMO capable of maintaining oxygenation and perfusion, allowing molecular studies that are unavailable in larger animal models. Fifteen C57BL/6 mice underwent ECMO by cannulating the left common carotid artery and the right external jugular vein. The mean arterial pressure was measured through cannulation of the femoral artery. The blood-primed circuit functioned well. Hemodynamic parameters remained stable and blood gas analyses showed adequate oxygenation of the animals during ECMO over a 1-hour timeframe. A significant increase in plasma-free hemoglobin was observed following ECMO, likely secondary to hemolysis within the miniaturized circuit components. Paralleling clinical data, ECMO resulted in a significant increase in plasma levels of multiple proinflammatory cytokines as well as evidence of early signs of kidney and liver dysfunction. These results demonstrate that this novel, miniature blood-primed ECMO circuit represents a functional murine model of ECMO that will provide unique opportunities for further studies to expand our knowledge of ECMO-related pathologies using the wealth of available genetic, pharmacological, and biochemical murine reagents not available for other species.

Cangrelor -Safe and Effective Agent for Treating Pump Thrombosis in LVAD Patients

Background Pump thrombosis (PT) is a major complication of Left Ventricular Assist Device (LVAD). One of the early markers of PT is elevation in Lactate Dehydrogenase (LDH). Aggressive anti coagulation regimen can sometimes decrease LDH levels and prevent surgical need for pump exchange. Several treatment strategies have been utilized including escalating anti thrombotic therapy. There is minimal data regarding the role of Cangrelor for treatment of PT. Purpose Cangrelor, which is a novel antiplatelet agent in the treatment of PT. Method Review of cases of suspected pump thrombosis as evidenced by elevated LDH and Plasma free hemoglobin, who were treated with Cangrelor at University Medical Center from October 2018 to March 2019. We found two cases that were treated with Cangrelor. Results First patient had Heart Mate implanted 02/01/2017. She had undergone pump exchange for pump thrombosis 03/16/2018. She was not a candidate for further pump exchange or transplant due to socioeconomic issues. She was admitted with elevated LDH of 1400. She was initially started on heparin and integrillin drips with no significant change in LDH for 3 days (1097,1466,1541). There was also ongoing increase in Plasma free hemoglobin (62,82, 107). At this point it was decided to discontinue Integrilin and start Cangrelor. The LDH level started decreasing immediately and was back to baseline level of nearly 600 in 4 days. Free hemoglobin normalized in 5 days. She had no major bleeding complications. She was discharged from the hospital without any major events. Second patient had Heart Mate II implanted January 2017. He had suffered subarachnoid hemorrhage, when treated with heparin and Integrilin drip for elevated LDH. He subsequently underwent LVAD exchange on 8/29/2018. Patient did well for few months after the pump exchange. However, he started having intermittent flash pulmonary edema, power fluctuations and was subsequently hospitalized for transplant evaluation. While admitted he was noted to have elevated LDH to more than 1000 with increase in plasma free hemoglobin. Due to his history of subarachnoid hemorrhage with Integrilin, we chose to use Cangrelor with standard dose heparin drip for treatment of pump thrombosis. He was initially given 4mcgm/kg/min with rapid reduction in LDH and free hemoglobin. He was then maintained on 0.75mcgm/kg/min. This dose was increased to 1.5mcg/kg/min as LDH started to rebound. Patient went on to get heart transplant and did well without any bleeding complications. Conclusions Cangrelor can be used along with heparin for pump thrombosis. It has been used effectively in decreasing the LDH levels without any major bleeding complications. It may be considered as safe alternative to other modalities of anticoagulation.

Hemolytic characteristics of three suctioning systems for use with a newly developed cardiopulmonary bypass system.

We have been developing a closed-circuit cardiopulmonary bypass (CPB) system ("Dihead CPB") for application during coronary artery bypass grafting (CABG) and valve surgery. To strive for minimal hemolysis during Dihead CPB, we compared the hemolysis caused by three different suction systems and performed a clinical study with the newly applied suction system. We evaluated the hemolysis caused by roller-pump suction, the SmartSuction® Harmony® and wall suction systems with respect to suction speed and compared the systems by means of in vitro studies. A clinical study was also performed on 15 volunteers to assess hemolysis and the adequacy of the newly applied suction system with Dihead CPB. Pressure inside the suction cannula was -22.5 ± 0.1 mmHg at a maximum flow of 1.5 L/min for roller-pump suction and -43.4 ± 0.1 mmHg at -150 mmHg of the set vacuum pressure of wall suction. With the SmartSuction, the pressure inside the cannula varied from -76.3 ± 1.0 to -130.3 ± 1.5 mmHg, depending on suctioning conditions. Suction speed (to suction 50 ml of blood) was fastest with the SmartSuction (69.7 ± 3.58 s) whereas, with roller suction, it was 117.3 ± 8.47 s and with wall suction 96.9 ± 7.10 s. The SmartSuction had the highest hemolysis rate (2.00 ± 0.33%) vs. 0.61 ± 0.10% for roller suction and 0.41 ± 0.11% for wall suction (p<0.001). The clinical study with wall suction showed no significant increase in plasma free hemoglobin during or after CPB compared with before surgery. Wall suction had less hemolysis than roller suction or the SmartSuction in the in vitro study and the clinical study with wall suction showed efficient suction speed and acceptable hemolysis, suggesting that Dihead CPB with wall suction is feasible for CABG.

In Vitro Hemocompatibility Evaluation of Ventricular Assist Devices in Pediatric Flow Conditions: A Benchmark Study.

Development of pediatric ventricular assist devices (VADs) has significantly lagged behind that of adult devices. This frustrating reality is reflected by the fact that the Berlin Heart EXCOR VAD is currently the only approved pediatric-specific device in the USA. An alternative option is an off-label use of adult continuous-flow VADs, such as HeartMate II (HMII), which inevitably causes patient-device size mismatch in small children. We sought to conduct in vitro hemocompatibility testing in a pediatric flow condition, with a specific aim to provide benchmark values for future pediatric device development. Given the aforementioned fact that both pulsatile and continuous-flow devices are being used in the pediatric population, we opted to test both types of devices in the present study. The EXCOR and HMII blood pumps were tested using bovine blood under constant hemodynamic conditions (flow rate, Q = 2.5 ± 0.25L/min; differential pressure across the pump, ΔP = 68 ± 5mm Hg). Hemolysis was measured by Harboe assay. There was a steady increase in plasma free hemoglobin during in vitro testing, with a statistically significant difference between 5 and 360 min for both EXCOR (P < 0.0001) and HMII (P < 0.001). However, the degree of an increase in plasma free hemoglobin was more significant with HMII (P < 0.001). Normalized index of hemolysis for EXCOR and HMII were 0.003 ± 0.0026g/100 L and 0.085 ± 0.0119g/100 L, respectively. There was also a steady increase in platelet activation detected by CAPP2A antibody using flow cytometry, with a statistically significant difference between 5 and 360 min for both devices (P < 0.05). The degree of an increase in platelet activation was similar between the two devices (P = 0.218). High molecular weight von Willebrand factor (HMW vWF) multimer degradation measured by immunoblotting was evident for both devices, however, it was more pronounced with the EXCOR. EXCOR blood samples from all three time points (120, 240, and 360 min) were significantly different from the baseline (5 min), whereas only 360 min samples had a significant difference from the baseline with the HMII. In conclusion, we have observed similarities and differences in hemocompatibility profiles between the EXCOR and HMII, both of which are commonly used in the pediatric population. We anticipate the benchmark values in the present study will facilitate future pediatric VAD development.

The Effect of Compliant Inflow Cannulae on the Hemocompatibility of Rotary Blood Pump Circuits in an In Vitro Model.

Rotary blood pumps (RBPs) are used for mechanical circulatory support in heart failure patients but exhibit a reduced response to preload changes, which can lead to ventricular suction events. A passive control system, in the form of a compliant inflow cannula (IC), has been developed to mitigate suction, although this device may cause significant hemolysis. This study compared the incidence of mechanically induced hemolysis of two compliant IC designs (strutted and nonstrutted) with a rigid IC (control) in a blood circulation loop over 90min. The nonstrutted compliant IC introduced high frequency and high amplitude oscillations in RBP inlet pressure and RBP IC resistance. These oscillations were correlated with a significant increase in plasma-free hemoglobin (pfHb) and hemolysis: pfHb increased to 2.005±0.665g/L, while normalized index of hemolysis (NIH) and modified index of hemolysis (MIH) increased to 0.04945±0.01276g/100L and 4.0505±0.6589 after 90min (P<0.05). In contrast, the strutted compliant IC performed similar to the clinically utilized rigid IC and did not increase pfHb (0.300±0.090 and 0.320±0.171g/L, respectively) andrate of hemolysis (NIH 0.00435±0.00155 and 0.00543±0.00371g/100L; MIH 0.3896±0.1749 and 0.4261±0.2792, respectively) within the RBP circuit. These data indicated that strutted, compliant ICs meet the hemocompatibility of clinically used rigid ICs while also offering a potential solution to prevent ventricular suction events.

In Vitro Comparative Assessment of Mechanical Blood Damage Induced by Different Hemodialysis Treatments

Gradual deterioration of red blood cells (RBCs) due to mechanical stress (chronic hemolysis) is unavoidable during treatments that involve extracorporeal blood circulation, such as hemodialysis (HD). This effect is generally undetectable and does not generate any acute symptoms, but it leads to an increase in plasma free hemoglobin (fHb). There are no absolute safety levels for fHb increase, indicating the need for an empirical evaluation using comparative testing. The increase in fHb levels was investigated in vitro by applying double‐needle double‐pump HD (HD‐DNDP), a new modality in which arterial and venous pumps both run continuously. fHb was measured during typical and worst‐case simulated dialysis treatments (double‐needle single‐pump HD [HD‐DNSP], hemodiafiltration [HDF‐DN], single‐needle double‐pump HD [HD‐SNDP], and HD‐DNDP) performed in vitro using bovine blood for 4 h. Hemolysis‐related indices (fHb%; index of hemolysis, IH; and normalized IH) were calculated and used for comparison. The increase in fHb during either HDF‐DN or HD‐SNDP with Artis and AK200 dialysis machines was similar, while the fHb at the maximum real blood flow rate (Qbreal) at the completion of the HD‐DNDP treatment on Artis was higher than that for HD‐DNSP using a Phoenix dialysis machine (fHb % = 1.24 ± 0.13 and 0.92 ± 0.12 for the Artis machine with HD‐DNDP at Qbreal = 450 mL/min and Phoenix with HD‐DNSP at Qbreal = 500 mL/min, respectively). However, the fHb levels increased linearly, and no steep changes were observed. The increases observed during HD‐DNDP were the same order of magnitude as those for widely used bloodlines and treatment modes for delivering dialysis treatments. The observed results matched literature findings, and thus the measured fHb trends are not predicted to have clinical side effects. HD‐DNDP treatment with Artis does not merit any additional concern regarding mechanical stress to RBCs compared with that observed for routinely used dialysis treatments, bloodlines and machines. Although the in vitro measurement of the fHb increase in bovine blood does not allow a prediction of the absolute level of blood mechanical damage or the possible effects in humans, such measurements are valuable for assessing hemolytic harm by performing tests comparing the proposed treatment with existing devices.

Technical complications during veno-venous extracorporeal membrane oxygenation and their relevance predicting a system-exchange--retrospective analysis of 265 cases.

ObjectivesTechnical complications are a known hazard in veno-venous extracorporeal membrane oxygenation (vvECMO). Identifying these complications and predictive factors indicating a developing system-exchange was the goal of the study.MethodsRetrospective study on prospectively collected data of technical complications including 265 adult patients (Regensburg ECMO Registry, 2009-2013) with acute respiratory failure treated with vvECMO. Alterations in blood flow resistance, gas transfer capability, hemolysis, coagulation and hemostasis parameters were evaluated in conjunction with a system-exchange in all patients with at least one exchange (n = 83).ResultsValues presented as median (interquartile range). Patient age was 50(36–60) years, the SOFA score 11(8–14.3) and the Murray lung injury Score 3.33(3.3–3.7). Cumulative ECMO support time 3411 days, 9(6–15) days per patient. Mechanical failure of the blood pump (n = 5), MO (n = 2) or cannula (n = 1) accounted for 10% of the exchanges. Acute clot formation within the pump head (visible clots, increase in plasma free hemoglobin (frHb), serum lactate dehydrogenase (LDH), n = 13) and MO (increase in pressure drop across the MO, n = 16) required an urgent system-exchange, of which nearly 50% could be foreseen by measuring the parameters mentioned below. Reasons for an elective system-exchange were worsening of gas transfer capability (n = 10) and device-related coagulation disorders (n = 32), either local fibrinolysis in the MO due to clot formation (increased D-dimers [DD]), decreased platelet count; n = 24), or device-induced hyperfibrinolysis (increased DD, decreased fibrinogen [FG], decreased platelet count, diffuse bleeding tendency; n = 8), which could be reversed after system-exchange. Four MOs were exchanged due to suspicion of infection.ConclusionsThe majority of ECMO system-exchanges could be predicted by regular inspection of the complete ECMO circuit, evaluation of gas exchange, pressure drop across the MO and laboratory parameters (DD, FG, platelets, LDH, frHb). These parameters should be monitored in the daily routine to reduce the risk of unexpected ECMO failure.

Hemolysis in a laminar flow-through Couette shearing device: an experimental study.

Reducing hemolysis has been one of the major goals of rotary blood pump development and in the investigational phase, the capability of hemolysis estimation for areas of elevated shear stresses is valuable. The degree of hemolysis is determined by the amplitude of shear stress and the exposure time, but to date, the exact hemolytic behavior at elevated shear stresses and potential thresholds for subcritical shear exposure remain vague. This study provides experimental hemolysis data for a set of shear stresses and exposure times to allow better estimations of hemolysis for blood exposed to elevated shearing. Heparinized porcine blood with a hematocrit of 40% was mechanically damaged in a flow-through laminar Couette shear flow at a temperature of 23°C. Four levels of shear stress, 24, 592, 702, and 842 Pa, were replicated at two exposure times, 54 and 873 ms. For the calculation of the shear stresses, an apparent viscosity of 5 mPas was used, which was verified in an additional measurement of the blood viscosity. The hemolysis measurements were repeated four times, whereby all conditions were measured once within the same day and with blood from the same source. Samples were taken at the inlet and outlet of the shear region and an increase in plasma-free hemoglobin was measured. An index of hemolysis (IH) was thereby calculated giving the ratio of free to total hemoglobin. The results are compared with data from previously published studies using a similar shearing device. Hemolysis was found to increase exponentially with shear stress, but high standard deviations existed at measurements with elevated IH. At short exposure times, the IH remained low at under 0.5% for all shear stress levels. For high exposure times, the IH increased from 0.84% at 592 Pa up to 3.57% at the highest shear stress level. Hemolysis was significant for shear stresses above ∼600 Pa at the high exposure time of 873 ms.

Hyperbilirubinemia Complicating Plasma-Free Hemoglobin and Antifactor Xa Level Monitoring on Venovenous Extracorporeal Membrane Oxygenation

Optical spectrophotometric methods are used to detect both plasma-free hemoglobin and antifactor Xa level, so hyperbilirubinemia can interfere with the measurement of both the monitoring laboratory tests for extracorporeal membrane oxygenation (ECMO) due to similar absorbance wavelengths. We present a seven-year-old child with acute respiratory failure on venovenous ECMO who developed an acute increase in plasma-free hemoglobin and undetectable antifactor Xa level due to acute hyperbilirubinemia from hepatic dysfunction related to antifungal therapy.

Plasma-Free Hemoglobin Levels in Advanced vs. Conventional Infant and Pediatric Extracorporeal Life Support Circuits

Extracorporeal life support (ECLS) is a reliable method to support pediatric patients with reversible cardiorespiratory failure associated with congenital heart disease, respiratory insufficiency, or after cardiac surgery. In 2010, our institution adopted an infant/pediatric extracorporeal membrane oxygenation (ECMO) circuit that contains a magnetically levitated centrifugal pump, polymethylpentene oxygenator, and shorter tubing length (ECMO II circuit). Our prior circuit contained a nonocclusive roller pump, polypropylene oxygenator, venous compliance chamber, and hemoconcentrator (ECMO I circuit). A retrospective chart review comparing ECMO I and ECMO II daily plasma-free hemoglobin (PFH) values was conducted. We hypothesized that the PFH is similar between the two ECMO circuit groups. We reviewed medical records of children 3 years of age or younger weighing less than 13 kg who required ECLS between January 2008 and February 2012. PFH levels from 18 ECMO II patients were compared with levels in a retrospective group of an equal number of well-matched ECMO I circuit patients. There was no significant difference between ECMO I and ECMO II circuit groups regarding mean time on ECMO, age in days, and weight. There was also no significant difference in the group mean levels of PFH between ECMO I and ECMO II circuits. There was a significant increase in PFH with hours on ECMO (p &lt; .01) within and between both circuit groups (p &lt; .01) and a significantly greater increase in PFH with ECMO hours (p = .0091) in the ECMO I circuit group. Although there was no significant difference in average PFH with the change in ECMO II circuit technology, advancements such as the magnetically levitated blood pump and polymethylpentene gas exchange device has been associated with significantly fewer mechanical component change-outs (p = .0156) and less clots and fibrin build-up in the circuits (p = .0548).

Successful Treatment of Rotary Pump Thrombus With the Glycoprotein IIb/IIIa Inhibitor Tirofiban

Despite advances in blood pump technology, thrombus formation within left ventricular assist devices (LVADs) is a life-threatening complication with few therapeutic options. A 38-year-old woman who underwent rotary LVAD implantation as a bridge to cardiac transplant developed labile flows (4 to >10 liters), associated with power spikes (4 to 12 watts) and an increase in plasma free hemoglobin (0.86 g/liter), consistent with pump thrombus at Day 140 post-LVAD implantation, despite thromboprophylaxis with aspirin and warfarin. Within 12 hours of commencing an intravenous infusion of tirofiban at a rate of 0.1 mug/kg/min, there were signs of improvement of pump dysfunction, and complete resolution was evident at Day 4 with, stable flows, power consumption and normalization of plasma free hemoglobin. Tirofiban may be considered as an alternative thrombolytic treatment strategy in rotary pump thrombus to avoid the need for LVAD replacement.

Percutaneous Catheter Thrombectomy Device for Acute Pulmonary Embolism: In Vitro and in Vivo Testing

To evaluate a percutaneous pulmonary embolism (PE) thrombectomy catheter that aspirates, macerates, and removes thrombus. Nine in vitro tests were performed by using porcine thrombi at a PE test station that provides continuous fluid output of 2 L/min at a pressure of 50 mmHg. Macroembolization was defined as embolized particles larger than 1.5 mm in dimension; microembolization was defined as particles that range in size from 0.1 to 1.5 mm. In static in vitro tests, researchers measured plasma-free hemoglobin levels in a 36-year-old man to assess mechanical hemolysis. Investigational review board approval and informed consent were obtained. The Department of Agriculture, Veterinary Bureau, Bern, Switzerland approved in vivo tests. Researchers investigated device effectiveness in 10 pigs that developed cardiogenic shock but survived massive PE after injection of two or three porcine thrombi into the external jugular vein via a surgically implanted 24-F sheath. Pulmonary angiography and hemodynamic measurements, including mean aortic and mean pulmonary artery pressure, heart rate, and mixed venous oxygen saturation, were obtained at baseline, after embolization, and after thrombectomy. Repeated-measures analysis of variance was performed to compare hemodynamic measurements at baseline, after embolization, and after thrombectomy. Cardiovascular structures were examined at necropsy for rupture, perforation, dissection, or hemorrhage. During a mean aspiration time of 69 seconds +/- 19, thrombi were completely extracted from 14-mm test tubes, with an aspirated fluid volume of 201 mL +/- 64. Although no macroembolization was observed, microembolization was quantified at 1.9 g +/- 1.3. Catheter aspiration was not associated with an increase in plasma-free hemoglobin. In 10 animals, aortic pressure increased from 52 mmHg +/- 24 before thrombectomy to 90 mmHg +/- 32 after thrombectomy, mixed venous oxygen saturation increased from 48% +/- 19% to 61% +/- 12%, pulmonary artery pressure decreased from 33 mmHg +/- 9 to 22 mmHg +/- 4, and heart rate decreased from 162 beats per minute +/- 24 to 114 beats per minute +/- 14. We did not observe macro- or microscopic damage to treated or untreated cardiovascular structures. The PE thrombectomy device was highly effective, facilitating rapid reversal of cardiogenic shock without device-related complications.

Hemolytic potential of hydrodynamic cavitation.

The purpose of this study was to determine the hemolytic potentials of discrete bubble cavitation and attached cavitation. To generate controlled cavitation events, a venturigeometry hydrodynamic device, called a Cavitation Susceptibility Meter (CSM), was constructed. A comparison between the hemolytic potential of discrete bubble cavitation and attached cavitation was investigated with a single-pass flow apparatus and a recirculating flow apparatus, both utilizing the CSM. An analytical model, based on spherical bubble dynamics, was developed for predicting the hemolysis caused by discrete bubble cavitation. Experimentally, discrete bubble cavitation did not correlate with a measurable increase in plasma-free hemoglobin (PFHb), as predicted by the analytical model. However, attached cavitation did result in significant PFHb generation. The rate of PFHb generation scaled inversely with the Cavitation number at a constant flow rate, suggesting that the size of the attached cavity was the dominant hemolytic factor.

Comparison of the AngioJet Rheolytic Catheter to Surgical Thrombectomy for the Treatment of Thrombosed Hemodialysis Grafts

To compare the clinical effectiveness of the AngioJet F105 rheolytic catheter to that of surgical thrombectomy for the treatment of thrombosed hemodialysis grafts. This was a multicenter, prospective, randomized trial comparing technical success, primary patency, and complication rates. A total of 153 patients were enrolled: 82 patients in the AngioJet group and 71 patients in the surgical thrombectomy group. Patient follow-up was performed 24-48 hours, 1 month, and 6 months after the procedures. Technical success, as defined by the patient's ability to undergo hemodialysis treatment, was 73.2% for the AngioJet group and 78.8% for the surgical thrombectomy group (P = .41). The primary patency rates of the AngioJet group were 32%, 21%, and 15% at 1, 2, and 3 months, respectively. The primary patency rates for the surgical group were 41%, 32%, and 26% at 1, 2, and 3 months, respectively. This difference approached statistical significance (P = .053). The groups had similar complication rates-14.6% in the AngioJet group and 14.1% in the surgery group-although the surgery group had more major complications (11.3%). In the AngioJet group, there was a transient increase in plasma-free hemoglobin, which normalized within 24-48 hours. The AngioJet F105 catheter provides similar clinical results when compared to surgical thrombectomy for the treatment of thrombosed hemodialysis grafts. The difference in patency rates between these two techniques approached statistical significance. In addition, results of both thrombectomy methods were inferior to those suggested by the Dialysis Outcomes Quality Initiative guidelines.

Clinical Comparison of Pulsatile and Nonpulsatile Perfusion During Cardiopulmonary Bypass

Controversy exists concerning the utilization of pulsatile flow during cardiopulmonary bypass (CPB) with regard to improved patient outcomes. The purpose of the present study was to evaluate pulsatile perfusion in patients undergoing CPB in a clinical setting. Seventy patients undergoing open heart surgery for repair of valvular or congenital heart disease were prospectively entered into the study and were randomly assigned to either pulsatile perfusion (PP, n=35) or nonpulsatile perfusion (NP, n=35) groups. All patients received identical surgical, perfusion, and postoperative care. Study parameters included: rate of spontaneous cardiac conversion, inotropic drug use, urine output, skin temperature, platelet count, fibrinogen concentration, and plasma free hemoglobin level. There were no statistically significant differences seen in either preoperative or operative parameters between groups. The PP group had a significantly higher rate of spontaneous cardiac conversion, less inotropic drug use, earlier recovery of skin temperature, and higher urine output during CPB (908.8 ± 87.2 ml/hr vs. 606.1 ± 57.5 ml/hr, p &lt; .01). There were no significant differences in either platelet count or fibrinogen concentration between groups. There was a steady increase in plasma free hemoglobin during PP, which was not seen in the NP group (p &lt; .01). We conclude that the use of pulsatile flow resulted in improved patient outcomes in maintaining better renal function and preserving cardiac function in the early post-bypass period.

Rheolytic Thrombectomy with Use of the AngioJet-F105 Catheter: Preclinical Evaluation of Safety

A preclinical evaluation of the safety of the AngioJet-F105 rheolytic thrombectomy catheter. The AngioJet-F105 catheter uses multiple retrograde high-speed fluid jets impinging on a primary aspiration lumen to create a hydrodynamic recirculation vortex that traps and fragments adjacent thrombus, with simultaneous evacuation of the resulting debris through the aspiration lumen. The effect of the AngioJet on treated vessels was evaluated in 10 canines. Vascular integrity on histopathologic examination and endothelial coverage on scanning electron microscopic study were examined in 15 vessel segments treated with the AngioJet-F105 catheter, compared with four vessel segments subjected to the Fogarty balloon maneuver, and 10 untreated vessel segments. The size distribution of particulate debris, upstream and downstream, after thrombectomy was determined in a flow-circuit model simulating the superficial femoral artery. Aliquots from the downstream effluent were then injected into the renal arteries of two healthy canines. The device caused only minimal focal endothelial denudation and no significant deep injury. No significant difference in endothelial coverage occurred in AngioJet-treated vessel segments compared to untreated control vessels (mean +/- standard deviation: 88.0% +/- 7.9% vs 89.7% +/- 11.6%, P = .77). Vessels treated with the Fogarty balloon pullback maneuver had significantly less residual endothelial coverage (58.0% +/- 8.0%, P < .03). Particulate microemboli in the effluent of the flow model accounted for 12% of the initial thrombus volume (0% > 100 microm, 99.83% < or = 10 microm). Histopathologic evaluation of the four renal beds injected with the resulting debris demonstrated no signs of necrosis. A moderate transient increase in plasma-free hemoglobin occurred, with a mild corresponding decrease in hematocrit. The AngioJet-F105 catheter resulted in only mild and focal injury to the treated vessels. The vast majority of resulting particulate debris consist of microscopic particles, without significant ischemic effect.

Impact of Venous Catheters on Packed Red Blood Cells

This study was designed to test the hypothesis that there would be increased hemolysis, as indicated by an increase in plasma free hemoglobin and potassium, when packed cells were infused through small gauge percutaneous catheters (24 and 28 g, PC) compared with short catheters (24 g; SC). We were unable to study the 28 g PC because after 1 hour, at a flow rate of 10 ml/hr, only 2.4 ml packed cells were infused. There was a significant increase in plasma free hemoglobin when pre- and postinfusion values were compared (SC, p = 0.005; PC, p = 0.009), but a statistically significant increase in potassium only for the SC (p = 0.008). There were no significant differences between the catheters for either potassium or free hemoglobin. For either catheter the quantity of free hemoglobin transfused could potentially cause a significant rise in serum bilirubin and hemoglobinuria.

Thoughts and Progress

In recent years, extracorporeal membrane oxygenation (ECMO) has been used for treatment of neonates with respiratory failure. A prototype of a compact ECMO system for neonates was developed. A single-lumen catheter, inserted into the right atrium via a jugular vein, was used for withdrawal and infusion of blood through the catheter. An extracapillary flow hollow-fiber membrane lung made of microporous polypropylene has a total surface area of 0.6 m2. To prevent the increase of plasma free hemoglobin, the ratio of withdrawal/infusion is controlled by a microcomputer. The system is compact in size with a low priming volume (less than 90 ml), which allows for ECMO with no additional blood transfusions. Its potential application as a respiratory support system is evaluated in animal experiments. The total intermittent veno-veno bypass flow was 15-30 ml/min/kg. The O2 transfer rate was 20 ml/min and the CO2 transfer rate was 33 ml/min at a blood flow rate of 300 ml/min. The O2 and CO2 exchange with the ECMO system was efficient enough to eliminate the respiratory failure induced by mechanical ventilation. The increase in plasma free hemoglobin was only 4 mg/dl after 6 h of ECMO. The system was considered applicable to respiratory aid for neonates.

Clinical Evaluation of Autotransfusion During Liver Transplantation

The clinical suitability of intraoperative autotransfusion was evaluated in 25 patients undergoing orthotopic liver transplantation using a Cell Saver #4 (Haemonetics) with acid-citrate-dextrose anticoagulation. In the first 14 patients (phase 1), biochemical, hematologic, coagulation, and semiquantitative bacteriologic studies were performed from the collected blood, processed blood, and patients' blood before and after 500 mL of autotransfusion. The acid-citrate-dextrose solution produced adequate anticoagulation, and the system effectively removed most of the potassium, red blood cell fragments, plasma free hemoglobin, bilirubin, coagulation factors, platelets, and fibrin degradation products. Autotransfusion (500 mL) did not alter coagulation, electrolyte balance, and hematologic findings in recipients except for a clinically insignificant increase in plasma free hemoglobin. Seventeen of 56 samples of the collected blood or processed blood were positive for coagulase (-) Staphylococcus (occasional or rare), but blood cultures before and after autotransfusion were negative in all patients. In the next 11 patients (phase 2), a quantitative bacteriologic study was performed from the collected blood, processed blood, skin, bile duct stump, peritoneal cavity, and room air using a mock reservoir. The processed blood was not transfused. All blood cultures from the patients were sterile. However, coagulase (-) Staphylococcus or Bacillus sp was seen in two cultures from skin, three from the processed blood, and three from air, suggesting that room air and skin were the sources of contamination. When the patients of the two phases of study were compared, postoperative blood cultures were all sterile, and renal function was similar. Therefore, autotransfusion appears to be clinically acceptable during liver transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of administrative vehicle on oral 1,1-dichloroethylene toxicity

The relationship between the acute toxicity and biologic fate of 1,1-dichloroethylene (1,1-DCE) was examined in fasted and fed male Sprague-Dawley rats given 200 mg 1,1-DCE/kg orally in a mineral oil, a corn oil, or an aqueous Tween-80 vehicle. Exhalation of unchanged 1,1-DCE by individual rats was monitored at selected 15-min intervals for 5 hr and all rats were sacrificed at 6 hr. The administrative vehicle affected the magnitude of liver injury in fasted rats; with mineral oil or corn oil, injury was massive [> 100-fold elevation of glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT)] whereas with the aqueous Tween-80 vehicle, injury was moderate t 15-fold elevation of GOT and GPT). In contrast, in all fed groups liver injury was slight (two- to threefold elevation of GOT and GPT). Rats with massive liver injury also had an ∼50-fold increase in plasma free hemoglobin and their kidneys exhibited numerous granular “heme” casts in Henle's loop without apparent degenerative changes in either glomeruli or tubular epithelium. No pathologic changes were observed in heart, lungs, spleen, adrenals, or duodenum. The administrative vehicle did not affect the total amount of 1,1-DCE exhaled, which was approximately half the given dose, nor did the vehicle affect the initial rapid phase of 1,1-DCE exhalation, which lasted ∼1 hr and had t 1 2 values ranging from 15 to 21 min for the fasted groups and from 10 to 13 min for the fed groups. In contrast, the later slow phase of 1,1-DCE exhalation was predictably affected by the administrative vehicle; t 1 2 values for the fasted and fed groups, respectively, were most prolonged with the poorly absorbed mineral oil vehicle (257 and 280 min), intermediate with the more digestable corn oil vehicle (73 and 103 min), and briefest with the more absorbable aqueous Tween vehicle (22 and 42 min). Further studies are needed to determine if the relative resistance of the fed animals to hepatic injury is due to the capacity of these animals to detoxify 1,1-DCE for a longer duration than the fasted animals.